dc.contributor.author | Senior, NJ | |
dc.contributor.author | Sasidharan, K | |
dc.contributor.author | Saint, RJ | |
dc.contributor.author | Scott, AE | |
dc.contributor.author | Sarkar-Tyson, M | |
dc.contributor.author | Ireland, PM | |
dc.contributor.author | Bullifent, HL | |
dc.contributor.author | Rong Yang, Z | |
dc.contributor.author | Moore, K | |
dc.contributor.author | Oyston, PCF | |
dc.contributor.author | Atkins, TP | |
dc.contributor.author | Atkins, HS | |
dc.contributor.author | Soyer, OS | |
dc.contributor.author | Titball, RW | |
dc.date.accessioned | 2018-11-12T15:04:26Z | |
dc.date.issued | 2017-07-21 | |
dc.description.abstract | BACKGROUND: The World Health Organization has categorized plague as a re-emerging disease and the potential for Yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. Environmental temperature is a key signal which regulates virulence of the bacterium. The bacterium normally grows outside the human host at 28 °C. Therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °C is central to the development of vaccines or drugs for the prevention or treatment of human disease. RESULTS: Using a library of over 1 million Y. pestis CO92 random mutants and transposon-directed insertion site sequencing, we identified 530 essential genes when the bacteria were cultured at 28 °C. When the library of mutants was subsequently cultured at 37 °C we identified 19 genes that were essential at 37 °C but not at 28 °C, including genes which encode proteins that play a role in enabling functioning of the type III secretion and in DNA replication and maintenance. Using genome-scale metabolic network reconstruction we showed that growth conditions profoundly influence the physiology of the bacterium, and by combining computational and experimental approaches we were able to identify 54 genes that are essential under a broad range of conditions. CONCLUSIONS: Using an integrated computational-experimental approach we identify genes which are required for growth at 37 °C and under a broad range of environments may be the best targets for the development of new interventions to prevent or treat plague in humans. | en_GB |
dc.description.sponsorship | This work was funded by the Defence Science and Technology Laboratory, award DSTLX-1000060221 (WP1). | en_GB |
dc.identifier.citation | Vol. 17, article 163 | en_GB |
dc.identifier.doi | 10.1186/s12866-017-1073-8 | |
dc.identifier.uri | http://hdl.handle.net/10871/34729 | |
dc.language.iso | en | en_GB |
dc.publisher | BMC | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/28732479 | en_GB |
dc.rights | © The Author(s). 2017. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | en_GB |
dc.subject | Essential genes | en_GB |
dc.subject | Metabolic model | en_GB |
dc.subject | Plague | en_GB |
dc.subject | TRADIS | en_GB |
dc.subject | Transposon | en_GB |
dc.subject | Yersinia pestis | en_GB |
dc.subject | Bacterial Proteins | en_GB |
dc.subject | Computational Biology | en_GB |
dc.subject | Gene Expression Regulation, Bacterial | en_GB |
dc.subject | Genes, Essential | en_GB |
dc.subject | Humans | en_GB |
dc.subject | Mutation | en_GB |
dc.subject | Plague | en_GB |
dc.subject | Yersinia pestis | en_GB |
dc.title | An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-11-12T15:04:26Z | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version. Available from BMC via the DOI in this record | en_GB |
dc.description | Availability of data and materials:
The datasets supporting the conclusions of this article are available at the NCBI GEO website https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100226. | en_GB |
dc.identifier.journal | BMC Microbiology | en_GB |